The relationship between aging and carcinogenesis was explored by transforming cultured cells derived from various sources with oncogenes. To mimic the in vivo state, we prepared primary culture cells from lung and skin tissues. Young and old rats were mainly used as donors. For in vitro studies fibroblasts from human fetal lung and rat whole embryos were passaged to appropriate population doublings. Cells were transfected with the calcium phosphate precipitated oncogene DNA then subjected to a focus assay. The number of foci, which indicate the number of transformed cells, were examined to determine if older cells respond differently to the oncogenes than younger cells. Our results indicate that cellular aging alters the intrinsic susceptibility to oncogene induced neoplastic changes at the cellular level.